Statin Treatment and 3′ Polyadenylation of eNOS mRNA

• DOI: 10.1161/atvbaha.107.154492
• Publication Date: 2007-10-05T01:18:37Z
• Authors: Ioanna Kosmidou; Jeffrey P. Moore; Martina Weber; Charles D. Searles
• Keywords: Cytochalasin D

Objective— Statins have been shown to increase endothelial nitric oxide synthase expression via enhanced mRNA stability. Because the poly(A) tail is an important determinant of transcript stability, we sought characterize effect statins on eNOS 3′ polyadenylation. Methods and Results— Endothelial cells treated with had a time- dose-dependent in transcripts long tails (75 160 adenosines). This was dependent 3-hydroxy-3-methylglutaryl (HMG)-coenxyme A (CoA) reductase inhibition observed both lipophilic (simvastatin) hydrophilic (rosuvastatin) statins. In stability assays, polyadenylated from statin-treated were 2- 3-fold more stable than untreated cells. The polyadenylation related cytoskeleton organization; there increased after Rho cytochalasin D treatment. Further, found phosphorylation RNA polymerase II cells, suggesting that statin-induced involved modulation activity. Conclusions— Our data provide insight into mechanism by which enhance protein: through Rho-mediated changes actin cytoskeleton.